We report a 42-year-old patient with progressive muscle weakness and motor difficulties from first decade of life. He was unable to run, jump or hop and had difficulty in climbing stairs. He was also unable to whistle. On examination he had ptosis but no winging of scapula. He was globally weak, with both proximal and distal muscle weakness. Distal weakness was worse than proximal in both upper and lower limbs. He maintained independent mobility which is consistently deteriorating. His cardiac and respiratory status is stable with no active interventions needed. Investigations showed that creatinine kinase levels were normal, and his neurophysiologic study showed myopathic features. He had been investigated with muscle biopsy both as a child and as an adult leading to no conclusive diagnosis. Molecular studies revealed shortened D4Z4 fragments in the patient establishing the diagnosis of facioscapulohumeral muscular dystrophy (FSHD). Under the assumption of a second disease mechanism, as the phenotype was atypical, with no classic features of winging of scapula or positive Beevor sign further investigations were done. He was heterozygous for the variants in TTN, MEGF10 and RYR1 genes identified on myopathy panel. Eventually, whole genome sequencing identified that he has biallelic pathogenic changes in MYPN gene confirming the diagnosis of congenital myopathy-24 along with FSHD. Our report highlights the power of whole genome sequencing in identifying the mutation responsible for the phenotype in this gentleman and suggests that “double trouble” of conditions with overlapping clinical features.

Myotonic dystrophy type 1 (DM1) is the commonest muscular dystrophy seen in adults. It is a trinucleotide repeat disorder. The expansion occurs at the end of the DMPK gene, in the 3′ untranslated region. DMPK is located on the long arm of chromosome 19 and codes for myotonic dystrophy protein kinase, a protein expressed predominantly in skeletal muscle. 1 DM1 is a multisystem disease and causes respiratory compromise, cardiac arrythmias and dilated cardiomyopathy in rare cases, endocrine disturbance, gastrointestinal problems including dysphagia and gut transit, cognitive difficulties, cataracts, and progressive skeletal muscle weakness and wasting as well as myotonia. The mean age of death is still approximately 58 years. Following a recent round table discussion to review national guidelines for myotonic dystrophy, the palliative care group reviewed the availability and access to palliative care and advance care planning. There is growing awareness of the value of palliative care support for DM1 patients. As part of this review, we published ‘the Oswestry model; DM1 adapted’ to enable teams to identify those patients more at risk of dying and in need of palliative care and an advance care plan (ACP). NeMO, neuromuscular at Oswestry, is a centre of excellence for neuromuscular care and we provide a symptom control clinic covering part of the West Midlands and North Wales area. This covers a population of approximately 6 million. The model of the clinic is quarterly reviews with the Palliative Care Consultant and Neuromuscular (NM) Specialist Nurse with other appropriate professionals as required. The patients are identified at NM clinics and multidisciplinary team (MDT) palliative ‘traffic light’ reviews. Choice of access to clinics includes face to face, telephone and virtual. We present the data from 2016-2023 (clinic started in 2016) including the mortality data, the uptake of ACP's and the experience of using the ‘Oswestry model; DM1 adapted’ tool.

Duchenne muscular dystrophy (DMD) is a severe, progressive, muscle-wasting, life limiting condition that affects just under 20 in every 100 000 live male births around the world. There are currently around 2500 boys and men living with the condition in the UK. DMD is caused by a mutation in the Dystrophin gene located on the X chromosome and causes progressive muscle wasting and weakness, both skeletal, but also affects respiratory muscles requiring support with ventilation and cardiac muscle resulting in a progressive dilated cardiomyopathy and cardiac arrhythmias in some patients. Following the publication of the cardiac care paper by Bourke et al. in 2022, we reviewed our DMD adult patients in our neuromuscular centre. NeMO, neuromuscular at Oswestry, is a centre of excellence for neuromuscular care and we provide a ‘one stop shop’ approach for patients attending clinic in the West Midlands and North Wales area. This covers at least a population of 6 million. At these appointments they receive all their neuromuscular assessments as required in one appointment, including cardiac ECHO and cardiology consultant opinion. Cardiac MR is arranged at a separate appointment if required clinically and can be tolerated. The cardiac paper by Bourke et al. compliments the international standards of care tripart publication by Birnkrant et al. and contains a clear pathway for UK specialists on how to preserve cardiac function and the further monitoring and management of DMD patients and carrier females. We therefore present the results of 26 DMD patients aged between 16 years and 40 years, with at least 2 time points for cardiac assessment; outcomes from the assessments as per guidelines, treatment regimes, and documentation of advanced care planning and implementation.

Spinal muscular atrophy (SMA) is a rare neuromuscular condition, characterised by loss of motor neurons due to a mutation in the survival motor neuron (SMN1) gene. Over the recent years there has been a dynamic shift in the therapeutic options for these patients involving both approved therapies, including gene therapy, and access to clinical trials in genetic modifying. As a result of this mortality and morbidity have changed, particularly for the SMA type 1 population, there has been a changing phenotypes with many children and therefore needing interventions at different time points compared to the natural history. This review process is a retrospective review from 1st July 2017 – 30th June 2022, the time when most of the new drug therapies were being introduced, of all the children aged from 0-16 years in the West Midlands region and their outcomes. The West Midlands population is approximately 6 million (8.85% UK population) and of that about 19% are aged between 0-16 years. In collaboration between The Robert Jones and Agnes Hunt Orthopaedic NHS Foundation Trust and University hospital Birmingham, the two tertiary centres for neuromuscular care and treatments in the West Midlands, we have reviewed all the patients that fulfil the study criteria and report the results of both disease trajectory, effect of ethnicity (20.6% of West Midlands population is Asian, Black or mixed ethnic group) on outcomes. The study includes the complete SMA patient population known to the West Midlands services during 1st July 2017 – 30th June 2022 that meet the eligibility criteria, aged between 0-16 years and including having had at least 2 clinical reviews in the time period. A minimum of 30 patients are expected to be recruited with full datasets. Results will be presented with patients who have had one or more of the 3 disease modifying therapies available and outcomes of those that have switched/combination therapies, including follow-up studies and specific cohorts discussed.

NeMO, neuromuscular at Oswestry, is a centre of excellence for neuromuscular care and we provide full multidisciplinary care for patients in the West Midlands and North Wales. This covers a population of 6 million. Many patients are high risk and travel long distances, up to 3 hours travel time, if rural. In July 2019 NeMO launched a new service called 'mobile muscle clinic' that was approved by the Trust's Ideas scheme. This coincided with the increase in spinal muscular atrophy (SMA) patients surviving on disease modifying treatments (DMT) and represented a ‘fragile’ and ‘high risk’ group. Regular follow up of these patients is crucial for maintaining, monitoring, and improving health, but frequent travel to clinic was seen as unsafe if they were on prolonged ventilation or needing mechanical suction of oral secretions. This ‘mobile muscle’ service involves a home visit by multidisciplinary team (MDT) for high-risk patients and only offered to patients who are at risk of deterioration without input from the muscle professionals. Whilst initially this service was more for the new SMA cohorts, it serves both paediatric and adult patients with high-risk neuromuscular disorders. At visit, the MDT provides clinical observations, blood tests, spirometry and 24 hr ECG monitors if needed, in addition to physiotherapy assessments and clinical advice. Since 2019 this service is regularly evaluated, and the audit loop completed in 2023. A questionnaire proforma was given to parent/carer for completion. The specialist nurse oversaw collecting the data. All professionals performing the home visit validated the feedback. Our results show that most of our patients are satisfied with the pre-visit organisation, visit discussion and outcome of visit. We report on the 4-year prospective data collection and the key findings will be presented. This understanding helps to improve quality of our service and we share our experience with other service providers.

Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disorder causing progressive muscle weakness resulting in permanent disability, which demands lifelong management. Care standards are required to ensure equitable care and measure improvement in FSHD services. However, these are currently lacking in the UK (UK) leading to service and care provision variability across the country, disparities in terms of care quality, and health inequalities, further exacerbated by financial and resource constraints. These deficiencies underscore the urgent need to establish benchmarks for UK clinical services that reflect the needs of both care providers and recipients, including people with FSHD, their families, and caregivers. Therefore, this study aimed to collaboratively develop care quality standards for FSHD, with people with FSHD, caregivers, and healthcare professionals, through qualitative focus groups. A two-stage process was used, comprising of 1) eight online focus groups with separate groups of people with FSHD, caregivers, and healthcare professionals (June – July 2023) and 2) two online focus groups bringing together people with FSHD, carers and healthcare professionals to refine initial findings and co-produce FSHD care standards (April 2024). Participants meeting the following inclusion criteria were included in the study: adults living with FSHD in the UK, informal carers of people with FSHD living in the UK, and UK healthcare professionals working with FSHD. Focus group transcripts were analysed using thematic analysis. Preliminary findings for agreed standards are reported here. Findings of preliminary analysis, which included 27 adults with FSHD, four caregivers, and 20 healthcare professionals from different professional backgrounds (e.g., neurologists, physiotherapists, care advisors, orthotists, psychologists) predominantly based in UK tertiary specialist centres, identified the following 11 care quality domains: education and support for people with FSHD at diagnosis; information, education and support for families and carers; support networks, forums and self-help groups; multidisciplinary team; periodical multidisciplinary review and clinical assessment; self-management; access to healthcare professionals with FSHD understanding; named healthcare professional; coordinated care and clinical pathways; service access modalities; communication. The preliminary framework emerging from these findings holds significant potential to shape the development of FSHD care standards, which can enhance care delivery, standardise practices, guide healthcare professionals’ education and training, mitigate regional discrepancies and health inequalities, and optimise FSHD patient health outcomes, not only within the UK but also globally. Importantly, anecdotal evidence suggests that current UK clinical services may fall short of meeting these standards, necessitating further action to bridge the existing gaps. Moving forward, this preliminary framework lays the groundwork for developing an audit tool to formally assess the alignment of UK clinical services with established care quality standards. As UK clinical services providing care for FSHD also manage other neuromuscular conditions, the implications of our findings extend beyond FSHD alone. Suboptimal care quality identified suggests broader challenges in neuromuscular care provision, emphasising the critical need for comprehensive care standards and quality improvement initiatives across neuromuscular services in the UK, with potential implications for global neuromuscular healthcare.

Objective: The Sars-Cov-2 pandemic and subsequent Government \u0027lockdown\u0027 has meant that boys with Duchenne Muscular Dystrophy (DMD) have not being seen in clinic for assessments and their North Star Ambulatory Assessment (NSAA) not administered The NSAA is a validated and reliable 17-item functional rating scale and widely used to assess motor function in DMD boys The standards of care recommend that DMD boys are seen every 6 months to assess function using the NSAA The aim is to investigate whether the NSAA could be used to accurately and reliably score ambulant boys with DMD by video assessment Methods: Ten ambulant DMD boys were selected from electronic hospital records at the Robert Jones Avisit two 21 8 (5 3) The two Physiotherapist video mean NSAA scores were 20 6 (5 66);Physiotherapist 1 and 20 6 (6 53) Physiotherapist 2 Decline in score from face-to-face visit one (12 months) to video assessment was 2 1 (3 09) This is consistent with the results of Mazzone et al (2011) where a mean decline in 12 months of 2 2 (3 7) was observed in 106 DMD boys Conclusion: The results from the study suggest that video NSAA is accurate and reliable However further studies with a larger cohort would need to be conducted to confirm these findings

Study design This is a retrospective longitudinal review. Objective The purpose of this review was to identify predictors of developing clinical scoliosis and compare between traumatic and neurological aetiologies of SCI. Setting This study was conducted at the Midland Centre of SCI. Method Case notes of all patients injured at an age up to 18 years and admitted between 1971 and 2013 were reviewed. Results Sixty-nine individuals were identified, of which seven were excluded: three with pre-existing scoliosis and four with spina bifida. The remaining 62 (44 males, 18 females) had a median age at injury of 17 years (inter quartile range 13-17). Of these, 51 (82%) had traumatic and 11 (18%) had neurological injury. Most (42/51; 82%) of the children who had a traumatic injury were older than 13 years. The risk of developing scoliosis was lower for older patients (RR 0.68 per year, 95% CI 0.52-0.83) or following a traumatic injury (RR 0.36, 95% CI 0.20-0.66). A multivariable analysis based on age and trauma showed that only older age decreased the risk. A robust Receiver Operator Curve analysis suggested 14.6 years as the optimal threshold to predict development of scoliosis within 10 years (Area Under the Curve; AUC 0.83 (95% CI 0.73-0.93), sensitivity 70% (95% CI 50-89%), specificity 89% (95% CI 74-100%). Conclusion Our results suggest that age below 14.6 years was a predictor for scoliosis. Once adjustment is made for age, the incidence of scoliosis does not differ between traumatic and neurological aetiologies of paediatric SCI injury.

Mutations the KHLH40 gene are a frequent cause of severe autosomal recessive neonatal nemaline cases. The KHLH40 gene (Kelch-like family member 40 gene) mutations have been found to be a relatively common cause of the severe nemaline myopathy, in particular in the Japanese population, accounting for 28% of cases. The striated-muscle-specific protein has been shown to be absent in these cases of KHLH40-associated nemaline myopathy skeletal muscle. It plays an important part in muscle development and function and therefore should be suspected in severe cases of nemaline myopathy with contractures and pre-natal symptoms. We describe a family who presented with three children affected with severe neonatal presentations, the two previous siblings clinically had nemaline myopathy but with no genetic diagnosis and died within the neonatal period. 7 years later the third child affected clinically with nemaline myopathy presented and we have subsequently confirmed genetically that all three cases were caused by mutations in the KHLH40 gene. The family have 2 unaffected children and the third baby with nemaline myopathy is now 7 months old supported with non-invasive ventilation during sleep and gastrostomy fed. Clinical features will be described in detail. The children were all found to be compound heterozygotes, with a mutation in the KLHL40 gene; c.434_435delGCinsAA p.(Cys145Ter), this variant results in a premature termination of the KLHL40 protein and therefore pathogenic, the second KHLH40 c.557T>A p.(Leu186His) sequence variant has not been previously described. It affects a highly conserved amino acid and in silico analysis predicts that this variant will affect the function of the KHLH40 protein. The cases are described in detail along with the muscle biopsies in two of the cases.

Mutations in the gene TPM3 (alpha-tropomysin (slow)) is a rare cause of nemaline myopathy Tropomyosin proteins regulate muscle contraction by controlling the binding of two muscle proteins, myosin and actin. Slow muscle α-tropomyosin is found only in type I fibers. Our case was given a diagnosis of ‘mild muscular dystrophy’ in 1968 when he was 18 years old. At that time, he was toe walking, unsteady on his feet and had pes cavus with demonstrable distal weakness. He represented at the age of 55 years with increasing difficulties climbing stairs and slopes and noticed his balance had deteriorated and he had developed a high stepping gait. He also reported weakness in his grip but was able to do buttons and undo bottle tops without too much difficulty. He reported that his mother, who had subsequently died, had had clawed toes and he had no siblings. He had obvious proximal limb girdle weakness and more marked distal weakness and a creatine kinase level that was mildy raised at 300 IU/L, neurophysiology confirmed a sensory axonal neuropathy and his muscle biopsy is discussed. His initial muscle biopsy showed variation in fibre size, increased internal nuclei and excessive connective tissue at age 18 years. Semithin sections were reviewed; his biopsy showed wide variation in fibre size, many atrophic fibres and some with severe fibrillar disorganisation. Large clusters of nemaline rods are striking. Sparse abnormal mitochondria are seen. Zebra fibres are sparsely seen, mainly in regions of fibrillar disorganisation. No collections of actin filaments are seen. We present an unusual case of TPM3 myopathy and the unusual muscle biopsy findings with Zebra bodies.

Heterozygous bicaudal D homolog 2 gene (BICD2) mutations cause a form of autosomal dominant spinal muscular atrophy with lower extremity predominance (SMALED). We describe the clinical phenotype, imaging and pathological features in 2 children (a boy and a girl) with BICD2 related SMALED. The first child was born with lower limb arthrogryposis with marked contractures at hips, knees and ankles. She had marked lower limb wasting and weakness with mild scapular winging and weakness in the axial and shoulder muscles. Reflexes were absent in legs. She never achieved independent ambulation and now at the age of 16 years uses a powered chair for mobility. Her course has been non-progressive and complicated by several orthopaedic surgeries in her legs. She does not have any cognitive difficulties. Neurophysiology showed a classic neurogenic pattern. Muscle MRI at the age of 9 showed extensive bilateral and symmetrical fatty degeneration of all muscle groups in the thighs and the calves. She was identified to have a de novo c.565A > T p.(Ile189Phe) heterozygous pathogenic mutation in the BICD2 gene. In the second child, we identified a de novo BICD2 heterozygous variant, c.682G > T, p.Asp288Tyr with lower extremity dominant SMA phenotype. He had congenital foot deformity, muscle atrophy of the legs, and stable weakness mainly of ankle dorsiflexors and invertors. He is independently ambulant. He has brisk reflexes in the legs. There was no apparent sensory or brain dysfunction. A left Quadriceps muscle showed features of a classic neurogenic pattern. Leg muscle MRI showed bilateral atrophy within the vastus lateralis, rectus femoris, sartorius and deep biceps and in the legs, there was atrophy of the gastrocnemius and partial involvement of the tibialis anterior muscles bilaterally. These findings confirm the previously reported recognisable phenotype in children affected with SMALED due to BICD2 mutations. The presence of brisk reflexes in the context of neurogenic changes is of interest and is also observed in other types of SMALED.

X-linked Charcot-Marie-Tooth disease (CMT) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene. This gene has nerve specific P2 promoter that work synergistically with SOX10 and EGR2 genes to initiate transcription. Mutation in this region is known to cause Schwann cell dysfunction. A single large family of X linked peripheral neuropathy was identified in our practice. Next generation sequencing for targeted panel assay identified an upstream exon-splicing deletion identified extending from nucleotide c.-5413 to approximately - c.-49. This matches the sequence of 32 nucleotides at positions c.*218-*249 in the 3'UTR downstream of the GJB1 gene. The deleted fragment included the entire P2 promoter region. The deletion segregated with the disease. To our knowledge a deletion of the P2 promoter alone as a cause of CMT has not been reported previously.

Immunoglobulin-helicase-µ-binding protein 2 (IGHMBP2) mutations usually lead to spinal muscular atrophy with respiratory distress type 1 (SMARD1), where most infants die before 1 year of age. Individuals with the CMT2 (axonal neuropathy) phenotype have been described with slowly progressive weakness, wasting and sensory loss but no significant respiratory compromise. In the largest case series published (Houlden et al. 2014), none of the fifteen patients from 10 to 43 years with the CMT2 phenotype required respiratory support. We present a case of axonal neuropathy related to IGHMBP2 mutation with late onset diaphragmatic weakness at 11 years. A 6-month-old boy presented with late onset bilateral equinovarus deformities of feet. He had no significant movement at ankle and knee joints. Neurophysiology was consistent with an axonal neuropathy. He has two heterozygous variants in IGHMBP2 gene c.1156 > C in exon 8 and c.2747G > A in exon 14. These variants were inherited from father and mother respectively. The second variant has not been reported in the literature. He achieved walking at two years with support but had progressive distal and proximal weakness of both upper and lower limbs leading to wheelchair dependence at 8 years. He has developed scoliosis. Respiratory status was satisfactory at 10 years with annual respiratory review and sleep studies. Soon after his 10th birthday he developed recurrent respiratory tract infections and pleural effusion requiring drainage. His chest x ray had no evidence of diaphragmatic weakness. He was discharged home on air. He struggled to tolerate spinal brace for scoliosis. He had repeat sleep studies which identified bilateral diaphragmatic weakness. He is now established on non-invasive ventilation. His clinical condition has been stable and he is awaiting scoliosis repair. Our case emphasizes the importance of respiratory surveillance for patients with IGHMBP2 related axonal neuropathy patients.

Facioscapulorhumeral dystrophy (FSHD) is widely stated to be the third most common genetic disease of skeletal muscle, with an incidence of 1 in 20,000. Weakness of shoulder muscles is the most constant feature of this disease negatively impacting tasks of daily living hence affecting independence. At present there is no known cure. Generic exercise is considered 'not harmful', but its effectiveness is still unknown. The aim of this exercise was to understand views of patients for compliance with exercise programmes and understand the barriers for regular exercise. We performed an online survey which was distributed to all patients registered on the FSHD register, UK. The Online survey asked them about the impact of upper limb dysfunction and their experience of upper limb exercises. This was followed by a focus group addressing compliance and barriers to exercise programmes. We received 232 responses from the online survey. 92.6% responders are in agreement that upper limb exercise is necessary as upper limb dysfunction impacts daily living in 86.9% patients. 57.1% considered that arm cycling would be a feasible exercise. The focus group session echoed the need for a home based exercise programme as attending a regular gymnasium was not entertained by patients. In this particular group of patients pain, fatigue and lack of motivation were additional barriers identified for compliance with exercise programmes. These results have now been incorporated into a pilot home based exercise intervention study.